Synthesis And Photocatalytic Fluoroalkylation Modification Of Quinazoline

As an aromatic N-heterocyclic compound,Quinazoline is the core structure in numerous alkaloids and functional molecules.The synthesis of quinazolines has importantly supported the fields of medicine,material,life science etc.Fluorine atom has the largest electronegativity among known elements,and its atomic radius is relatively small.This unique structure makes that fluorine-containing compounds have attracted great attention with their features.Fluorine-containing compounds have special electronic effects,lipid solubility and metabolic stability in the fields of medicine and pesticide.Hence,this paper mainly realized the new synthesis of quinazolines,and explored the fluoroalkylation of quinazolines under visible light.The primary research contents were as follows:1.4-Methylquinazoline was successfully synthesized from the o-aminoacetophenone oxime,which was prepared by oximation of o-aminoacetophenone,in moderate yield with potassium bromodifluoroacetate as catalyst,N,N-Dimethylacetamide as carbon source and solvent,potassium carbonate as base.Then,the scope of this reaction was elucidated by using o-aminoacetophenone oximes with different functional groups.The structure of the products was characterized by NMR and IR.Based on the experimental data and references,the reaction mechanism was speculated.N,N-Dimethylamides were first used to provide carbon for aromatic heterocyclization,which provides a new strategy for the synthesis of aromatic heterocyclic compounds.2.The fluoroalkylation of quinazoline was explored by using visible light catalysis with the advantages of safety and efficiency.By searching the experimental conditions including difluoroalkylation and trifluoromethylation reagents,base,solvents etc,several fluoroalkyl substituted quinazolines were successfully synthesized in moderate yields.Then,the scope of this reaction was simplely elucidated by using quinazoline with different functional groups.The structure of the products was characterized by NMR,MS and IR.The photocatalytic difluoroalkylation and trifluoromethylation of quinazolines provide the new methods for fluoroalkylation of quinazolines.Fluoroalkylation products of quinazolines have potential application value in medicine,life science and other fields,because of their dual characteristics of quinazoline and fluorine-containing compounds.